Choroideremia

Choroideremia is a condition characterized by progressive vision loss that mainly affects males. The first symptom of this condition is usually an impairment of night vision (night blindness), which can occur in early childhood. A progressive narrowing of the field of vision (tunnel vision) follows, as well as a decrease in the ability to see details (visual acuity). These vision problems are due to an ongoing loss of cells (atrophy) in the specialized light-sensitive tissue that lines the back of the eye (retina) and a nearby network of blood vessels (the choroid). In people with choroideremia, the vision impairments get progressively worse and ultimately lead to blindness (decreased visual acuity or field of vision), typically in late adulthood.

The prevalence of choroideremia is estimated to be 1 in 50,000 to 100,000 people. This condition is thought to account for approximately 4 percent of all blindness.

Mutations in the CHM gene cause choroideremia. The CHM gene provides instructions for producing the Rab escort protein-1 (REP-1). As an escort protein, REP-1 attaches to molecules called Rab proteins within the cell and directs them to the membranes of various cell compartments (organelles). Rab proteins are involved in the movement of proteins and organelles within cells (intracellular trafficking). Mutations in the CHM gene lead to the production of a REP-1 protein that cannot carry out its protein escort function. This lack of functional REP-1 prevents Rab proteins from reaching and attaching (binding) to the organelle membranes. Without the aid of Rab proteins in intracellular trafficking, cells die prematurely.

The REP-1 protein is active (expressed) throughout the body, as is a similar protein, REP-2. It is thought that when REP-1 is nonfunctional, REP-2 can perform the protein escort duties of REP-1 in many of the body's tissues. Very little of the REP-2 protein is present in the retina, however, so it cannot compensate for the loss of REP-1 in this tissue. This loss of REP-1 function and subsequent misplacement of Rab proteins within the cells of the retina causes the progressive vision loss characteristic of choroideremia.

Choroideremia is inherited in an X-linked recessive pattern. The CHM gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene, but usually does not experience signs and symptoms of the disorder. Females who carry a CHM mutation may show small areas of cell loss within the retina that can be observed during a thorough eye examination. These changes typically do not impair vision.